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000280979 1001_ $$00000-0002-4028-1391$$aKruse, Sebastian$$b0
000280979 245__ $$aA versatile silica nanoparticle platform for induction of T cell responses – applied for therapeutic vaccination against HPV16 E6/E7-positive tumors in MHC-humanized mice
000280979 260__ $$aAbingdon$$bTaylor & Franics$$c2025
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000280979 520__ $$aTherapeutic vaccines represent a promising treatment option for (pre)cancerous lesions, such as human papillomavirus-induced malignancies. They act via administration of tumor-specific antigens, leading to induction of antigen-specific cytotoxic T cell responses. However, vaccination efficiency is often limited when the antigen is administered alone, due to antigen instability and inefficient uptake by antigen-presenting cells (APCs). To address these limitations, nanoparticle-based vaccine delivery systems are currently under investigation. Here, we present a novel silica nanoparticle (SiNP)-based vaccine delivery platform that can be applied for the treatment of various diseases and cancer types. We show that surface-functionalized SiNPs are non-cytotoxic and quickly taken up by APCs. Incorporation of a linker/solubilizer sequence N-terminal of the epitope allows attachment of peptides regardless of their solubility as well as efficient processing and surface presentation by APCs. Whole-body distribution studies confirmed retention of the antigen at the injection site and decelerated excretion when connected to SiNPs. Furthermore, treatment with SiNPs, especially when combined with the adjuvant poly(I:C), resulted in activation of dendritic cells capable of priming CD8+ T cells. In C57BL/6 and MHC-humanized A2.DR1 mice, the SiNP-based vaccinations induced epitope-specific CD8+ T cells. Moreover, they exhibited anti-tumor activity and provided a survival benefit in a tumor model using HPV16 E6/E7-expressing PAP-A2 cells. Thus, the novel SiNP platform represents a promising new vehicle for therapeutic vaccine delivery.
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000280979 7001_ $$00009-0002-9985-4227$$aFricke, Lia T.$$b1
000280979 7001_ $$00000-0002-9077-635X$$aZottnick, Samantha$$b2
000280979 7001_ $$00000-0003-1269-2537$$aSchlosser, Ann-Katrin$$b3
000280979 7001_ $$aGrabowska, Agnieszka K.$$b4
000280979 7001_ $$aFeidt, Eva$$b5
000280979 7001_ $$00000-0002-8616-5599$$aUhl, Philipp$$b6
000280979 7001_ $$aJunglas, Ellen$$b7
000280979 7001_ $$00000-0003-3437-6738$$aFörster, Jonas D.$$b8
000280979 7001_ $$0P:(DE-2719)9000491$$aBlersch, Josephine$$b9
000280979 7001_ $$0P:(DE-2719)2810245$$aDenner, Philip$$b10
000280979 7001_ $$00009-0002-5616-2589$$aGünter, Manina$$b11
000280979 7001_ $$00000-0003-4054-9041$$aAutenrieth, Stella E.$$b12
000280979 7001_ $$0P:(DE-2719)2159508$$aFava, Eugenio$$b13
000280979 7001_ $$00000-0002-3901-5061$$aMier, Walter$$b14
000280979 7001_ $$aKübelbeck, Armin$$b15
000280979 7001_ $$00000-0002-5865-0714$$aRiemer, Angelika B.$$b16
000280979 773__ $$0PERI:(DE-600)2645309-5$$a10.1080/2162402X.2025.2548002$$gVol. 14, no. 1, p. 2548002$$n1$$p2548002$$tOncoImmunology$$v14$$x2162-4011$$y2025
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